Post-translational modifications on RNA-binding proteins: accelerators, brakes, or passengers in neurodegeneration?

RNA-binding proteins (RBPs) are critical players in RNA expression and metabolism, thus, the proper regulation of this class of proteins is critical for cellular health. Regulation of RBPs often occurs through post-translational modifications (PTMs), which allow the cell to quickly and efficiently respond to cellular and environmental stimuli. PTMs have recently emerged as important regulators of RBPs implicated in neurodegenerative disorders, in particular amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here, we summarize how disease-associated PTMs influence the biophysical properties, molecular interactions, subcellular localization, and function of ALS/FTD-linked RBPs, such as FUS and TDP-43. We will discuss how PTMs are believed to play pathological, protective, or ambiguous roles in these neurodegenerative disorders.

Automated summary

RNA-binding proteins play critical roles in RNA expression and metabolism, and their proper regulation is essential for cellular health. Regulation of RBPs often occurs through post-translational modifications (PTMs), allowing cells to respond efficiently to various stimuli. Recent studies have shown that PTMs are important regulators of RBPs associated with neurodegenerative disorders like ALS and FTD, influencing their biophysical properties, molecular interactions, subcellular localization, and function. The roles of PTMs in these neurodegenerative disorders can be pathological, protective, or ambiguous.